This application addresses the broad Challenge Area "Comparative Effectiveness Research (05)" The specific Challenge Topic is "05-AG-104: Planning Grants and Pilot Studies for Comparisons of Management Strategies for Older Patients with Multiple Coexisting Conditions" This topic is further designated by NIA as the Institute's highest priority. End-stage renal disease affects less than 0.5% of the Medicare population, yet accounts for nearly 7% of Medicare expenditures. Despite considerable burden and expense, patients on dialysis experience unacceptably high mortality rates (in excess of 20% per year), exceptionally high rates of hospitalization (more than two hospitalizations per patient per year, spending on average a fortnight per year in hospital), and impaired functional status and health-related quality of life. We and others have highlighted the high rates of mortality, morbidity, disability, frailty and impaired functioning in the ESRD population. The degree to which poor health status results from kidney failure versus other associated diseases versus imperfections and complications of dialysis is unknown. We propose to conduct a pilot study to test the feasibility, safety and efficacy of conservative versus dialytic management in elderly persons with stage V chronic kidney disease (CKD). The Specific Aims are: To determine the feasibility of randomizing elderly (age >70 years) subjects with stage V chronic kidney disease (CKD) (estimated glomerular filtration rate (eGFR) 9 to <15 mL/min/1.73m2) to conservative management versus initiation of dialysis;To determine the relative safety of conservative versus dialytic management for patients with stage V CKD;and To determine the relative efficacy of conservative versus dialytic management for elderly patients with stage V CKD on multiple domains of health and well-being, including: health- related quality of life, symptoms and burden of advanced CKD, physical function, physical activity, cognitive function, mental health, nutritional and inflammatory status, body composition, blood pressure and pulse wave velocity, hospitalization rate and number of hospital days. The design of this pilot study will be a clinical trial, with randomization stratified by center (three centers affiliated with Stanford University. The conservative intervention will include careful attention to metabolic and other manifestations of advanced chronic kidney disease, with a transition to an attenuated dialysis prescription when the eGFR drops consistently below 9 mL/min/1.73m2. The dialytic intervention will include initiation of thrice weekly hemodialysis or conventional peritoneal dialysis following randomization. Both groups will receive monthly study visits with an investigator, research nurse coordinator and registered dietitian expert in kidney disease. Numerous domains of health status will be evaluated, and all medical events will be tracked. The study will focus principally on feasibility and safety, but the relative efficacy of conservative versus dialytic management strategies will also be compared. Since dialysis is emblematic of life-sustaining therapies, the potential impact of this study on science and health care extends beyond the sizable population of Americans with stage V CKD. Arguably, since ESRD disproportionately affects minority populations, particularly African Americans, the poor and the uninsured, this type of comparative effectiveness research can influence many of the most vulnerable of our citizens. We believe that this pilot trial could lead have a significant impact on health care policy. PUBLIC HEALTH RELEVANCE (provided by applicant): Patients with advanced chronic kidney disease (CKD) may or may not benefit from the initiation of dialysis in the absence of symptomatic uremia (accumulation of the bloodstream with by- products of metabolism). This pilot clinical trial aims to determine the feasibility, safety and efficacy of two alternative strategies - one in which patients with advanced CKD begin dialysis, and another in which a series of conservative measures are instituted and dialysis is deferred until there is further loss of kidney function. If this pilot trial demonstrates feasibility in randomizing patients to these two strategies, results from this pilot study can be used to inform the design of a larger, more definitive trial.